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Biomedical subjects

M Sakakibara

Publications and source records attributed to M Sakakibara.

At least 37 records · Page 2Linked to original sources

Mechanisms underlying the M-current block by barium in bullfrog sympathetic neurons.

Whole-cell/voltage-clamp recordings were made from dissociated bullfrog sympathetic neurons to examine the channel blocking actions of barium (3-2000 microM) on an M-type potassium current (I(M)). Barium (IC(50) approximately 105 microM) blocked I(M) without affecting the 50%-activation voltage ( approximately -35 mV) and the slope factor ( approximately 11 mV) of the activation curve. The results indicate that the barium block is independent of the kinetics of I(M).

Action Potentials↗

Ethanol production by repeated batch culture using yeast cells immobilized within porous cellulose carriers.

Ethanol was efficiently produced for 20 d by repeated batch culture using yeast cells immobilized in porous cellulose carriers. The physical structure of the carrier beads, which had small pores distributed on the outer surface and relatively large pores distributed in the interior, was found to be effective for cell immobilization. The effects of chemical modifications to the basic cellulose carrier on cell immobilization and ethanol production were also examined in repeated batch cultures. The chemical modifications had little effect on either cell immobilization or ethanol production.

Journal Article↗

Purulent pericarditis due to group B streptococcus and mycotic aneurysm of the ascending aorta: case report.

A 61-year-old female, with a history of uterine and cervical cancer treated with radical hysterectomy and 2 years of postoperative chemotherapy, presented to the emergency department with dyspnea on exertion. Computed tomography of the chest revealed a large pericardial effusion and a sacciform aneurysm of the ascending aorta. The patient subsequently underwent emergency pericardiocentesis with drainage of approximately 330 ml of a bloody and turbid effusion. Cultures from the effusion yielded group B streptococcus. Multiple organ failure and disseminated intravascular coagulation syndrome occurred in the acute phase, but gradually improved with continuous antibiotic therapy. On the 194th hospital day, in situ reconstruction of the ascending aorta was successfully performed using a synthetic graft. Although rarely reported, both purulent bacterial pericarditis and mycotic aneurysm can be life-threatening.

Aneurysm, Infected↗

Oleyl alcohol inhibits intestinal long-chain fatty acid absorption in rats.

Long-chain fatty acids are important nutrients, but obesity is the most common nutritional disorder in humans. In this study we investigated the effect of oleyl alcohol on the intestinal long-chain fatty acid absorption in rats. We administered [14C]oleic acid and oleyl alcohol as lipid emulsion intraduodenally in unanesthetized lymph-cannulated rats and measured the lymphatic output of oleic acid. Second, we orally administered lipid emulsion with a stomach tube and measured the luminal and mucosal oleic acid residues. Furthermore, rats were fed oleyl alcohol as a dietary component for 20 days, and fecal lipid and the weight of adipose tissues were measured. In lymph-cannulated rats, triglyceride and [14C]oleic acid output in the lymph were significantly lower in the presence of oleyl alcohol when compared with the absence of oleyl alcohol in a dose-dependent manner. The radioactivity remaining in the intestinal lumen was more strongly detected in rats that had been orally administered oleyl alcohol than in the controls. The feces of rats fed an oleyl-alcohol-added diet contained much higher amounts of lipids, and the weights of their adipose tissues were significantly lower than in the control group. These results suggest that oleyl alcohol inhibits the rat gastrointestinal absorption of long-chain fatty acids in vivo.

Adipose Tissue↗

Efficacy of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients aged > or = 80 years.

The therapeutic result of primary percutaneous transluminal coronary angioplasty (PTCA) in the elderly was assessed in 20 of 44 patients > or = 80 years old (range 81-92 years, mean age 84 +/- 3 years) with acute myocardial infarction who underwent primary PTCA and the results compared with 194 younger patients (< 80 years) who underwent primary PTCA during the same period. In-hospital prognosis, and long-term outcomes were investigated. Emergency coronary angiography was performed in 47.7% of the patients with acute myocardial infarction in the elderly group with 45.5% receiving primary PTCA. Primary PTCA was successful in 95.0% of the elderly group, showing no significant difference from the younger group. In-hospital mortality showed no significant difference between the elderly group and the younger group (5.0% vs 4.1%). However, the incidences of pump failure of the heart and bleeding complication requiring blood transfusion were higher in the elderly group during hospitalization. The 2-year survival rate for the elderly group was 82.5 +/- 9.3%, which was better than previous studies. These results suggest that primary PTCA has a good success rate in the elderly patients with acute myocardial infarction, and decreases the in-hospital mortality and improves the long-term outcome. However, this study was conducted retrospectively in a small group of patients. The efficacy of primary PTCA for the elderly remains to be clarified in a larger prospective trial.

Age Factors↗

[Different inhibiting effects of abciximab and tirofiban on platelet thrombus formation on a collagen surface under flow conditions].

OBJECTIVES: Recently developed anti-GPIIb/IIIa agents effectively inhibit acute thrombotic occlusion of coronary arteries after interventional treatment, and have similar inhibiting effects on plasma ligand binding to GPIIb/IIIa. Clinical investigation has revealed that abciximab, the chimeric monoclonal antibody against GPIIb/IIIa, has superior in vivo antithrombotic effects to other agents. The inhibiting effects of abciximab and another anti-GPIIb/IIIa agent, tirofiban, were investigated on platelet thrombus formation on a collagen surface under flow conditions. METHODS: Blood was drawn from 6 normal volunteers and anticoagulated with a specific inhibitor of thrombin, argatroban, at a final concentration of 100 microM. Platelets were rendered fluorescent by addition of mepacrine to a final concentration of 10 microM. Mepacrine is concentrated in the dense granules of platelets and leukocytes, but does not accumulate in red blood cells, so platelet thrombi can be detected by fluorescence microscopy even in the presence of red blood cells. Horizontal glass slips covered with fibrillar type I collagen were assembled in a Hele-Shaw type flow chamber. RESULTS: Platelet thrombi were developed on the collagen surface even in the absence of platelet activating agents. Both abciximab and tirofiban inhibited the platelet thrombus formation. Single platelet adhesion on the collagen surface was inhibited only by abciximab and not by tirofiban. CONCLUSIONS: The superior in vivo antithrombotic effects of abciximab may be partially explained by its inhibiting effects on the platelet adhesion on exposed subendothelial matrix.

Abciximab↗

Examination of microgravity effects on spontaneous Ca2+ oscillations in AtT20 pituitary cells using heavy water.

Effects of heavy water (D2O) on various organisms have been extensively studied and a majority of D2O actions were generally ascribed to the viscosity (1.23 times of H2O) and a larger inter-molecule force of D2O that may eventually alternate molecular structure of various enzymes and ion channels. It is reported that chronic application of D2O induces toxic effects and the 35% substitution of whole body water with D2O induced fatal effects in the mouse. Mitosis of a fertile egg of sea urchin was completely inhibited by 75% D2O but the paused segmentation was recovered after rinse of D2O. In addition, we also observed that neuronal development of the Lymnaea stagnalis was reversibly inhibited by D2O (M. Sakakibara, unpublished data). However, mechanism of the toxicity of D2O and the effects of D2O on cellular events have not been fully understood. The spontaneous oscillation in cytosolic free Ca2+ concentration is one of the typical physiological events in living secretory cells. We previously demonstrated that the Ca2+ oscillations are regulated by voltage-sensitive Ca2+ channels (VSCC), Ca2+ ATPases, and Ca(2+)-induced Ca2+ release from intracellular stores. To analyze the site(s) of action of D2O in the living cellular systems, the present study examined effects of D2O on the Ca2+ mobilization and resting membrane potentials in AtT20 mouse pituitary cells.

Animals↗

Identification of a prothoracicostatic peptide in the larval brain of the silkworm, Bombyx mori.

Prothoracicotropic hormone (PTTH) stimulates ecdysteroid biosynthesis in the prothoracic gland (PG) of insects. A peptide inhibiting ecdysteroid biosynthesis in the PG was isolated from the extracts of 2,000 larval brains of the silkworm, Bombyx mori, using a protocol that included four reversed-phase high performance liquid chromatography procedures. The primary structure of this prothoracicostatic peptide (Bom-PTSP) was determined to be H-Ala-Trp-Gln-Asp-Leu-Asn-Ser-Ala-Trp-NH(2). This neuropeptide has the same sequence as Mas-MIP-I, a myoinhibitory peptide previously isolated from the ventral nerve cord of the tobacco hornworm, Manduca sexta, and is highly homologous with the N-terminal portion of vertebrate peptides of the galanin family. This peptide inhibited PTTH-stimulated ecdysteroidogenesis in the PG at both the spinning and feeding stages, which indicates that Bom-PTSP interferes with PTTH-stimulated ecdysteroidogenesis.

Amino Acid Sequence↗

S1319: a novel beta2-andrenoceptor agonist from a marine sponge Dysidea sp.

In the course of screening of potential leads for beta2-receptor agonists, we found a novel beta2-adrenoceptor selective agonist, S1319, from a marine sponge Dysidea sp. The active compound was isolated and structurally characterized as 4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1,3-benzothiazole-2(3H)-o ne, a new member of the beta2-adrenoceptor agonist. This is the first example of a sponge-derived beta2-adrenoceptor agonist.

Adrenergic beta-2 Receptor Agonists↗

Membrane-type matrix metalloproteinase-1 expression and activation of gelatinase A as prognostic markers in advanced pediatric neuroblastoma.

BACKGROUND: Recently a novel membrane-type matrix metalloproteinase-1 (MT-MMP-1) was discovered to be a specific activator of progelatinase A, and was correlated with tumor invasion. To the authors' knowledge, no information regarding the expression of MT-MMP-1 has been reported in childhood malignancies. In this study, the authors attempted to elucidate the specific mechanisms that underlay the invasive behavior of neuroblastoma (NB) cells with respect to the expression of MT-MMP-1 and its determined prognostic value, especially in pediatric patients with advanced Evans' Stage IV NB. METHODS: Thirty specimens from surgically excised NB (mainly Stage IV) were collected retrospectively. The total levels of progelatinase A (68 kilodaltons [kD]) and its activated form (62 kD) in the tumor lysates were quantified by gelatin zymography. The expression of MT-MMP-1 was estimated by immunostaining with a monoclonal antibody (113-5B7). RESULTS: Progelatinase A and the activated form were detected in each of the 30 specimens. The gelatinase A activation ratio, 62 kD/(62 kD + 68 kD), strongly correlated with the high levels of MT-MMP-1 expression found in specimens of advanced tumor stage. In the patients with advanced Stage IV NB, the activation ratio was strongly associated with unfavorable clinical outcome; the 5-year survival was 88.9% in the patients with a low activation ratio (< or = 26%) versus only 21.2% in the patients with a high activation ratio (>26%). CONCLUSIONS: Gelatinase A activation correlates with high expression of MT-MMP-1 on NB cells and is associated strongly with advanced stage and poor clinical outcome. These results are consistent with the notion that MT-MMP-1 expression is an important prognostic determinant of the biologic behavior of NB.

Adolescent↗

Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding phenylacetaldehyde reductase from styrene-assimilating Corynebacterium sp. strain ST-10.

The gene encoding phenylacetaldehyde reductase (PAR), a useful biocatalyst for producing chiral alcohols, was cloned from the genomic DNA of the styrene-assimilating Corynebacterium sp. strain ST-10. The gene contained an opening reading frame consisting of 1,158 nucleotides corresponding to 385 amino acid residues. The subunit molecular weight was calculated to be 40,299, which was in agreement with that determined by polyacrylamide gel electrophoresis. The enzyme was sufficiently expressed in recombinant Escherichia coli cells for practical use and purified to homogeneity by three-column chromatography steps. The predicted amino acid sequence displayed only 20-29% identity with zinc-containing, NAD(+)-dependent, long-chain alcohol dehydrogenases. Nevertheless, the probable NAD(+)- and zinc-binding sites are conserved although one of the three catalytic zinc-binding residues of the zinc-containing, long-chain alcohol dehydrogenases was substituted by Asp in PAR. The protein contains 7.6 mol zinc/mol tetramer. Therefore, the enzyme was considered as a new member of zinc-containing, long-chain alcohol dehydrogenases with a particular and broad substrate specificity.

Alcohol Oxidoreductases↗

Tracheal relaxing effects and beta2 adrenoceptor selectivity of S1319, a novel sponge-derived bronchodilator agent, in isolated guinea-pig tissues.

1. S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1, 3-benzothiazol-2(3H)-one acetate), a novel non-catecholamine beta-adrenoceptor agonist, has been compared with isoprenaline, salbutamol and formoterol for activity in vitro on a range of beta-adrenoceptor containing preparations from guinea-pig. 2. S1319, like isoprenaline, salbutamol and formoterol, relaxed preparations of guinea-pig trachea (contracted by histamine) in a concentration-dependent manner. The relaxing activity of S1319 appeared to be more potent than that of isoprenaline and salbutamol, and similar to that of formoterol (pD2 values of 10.58+/-0.03 vs 7. 60+/-0.01, 7.50+/-0.01 and 10.52+/-0.04, respectively), and was blocked by the beta2-adrenoceptor selective antagonist (ICI 118,551). The intrinsic activity of S1319 was close to 1.0. 3. In the beta1-adrenoceptor containing preparations, guinea-pig right and left atria, a monophasic inotropic response of S1319 was observed. The pD2 value of S1319 for left atrial and right atrial inotropism was 6.70+/-0.15 and 7.81+/-0.01, respectively. 4. The selectivity ratio (trachea/left atrial inotropism) of S1319, formoterol, salbutamol and isoprenaline was 8523, 284, 4.8 and 0.45, respectively. The relative selectivity ratio of S1319 was 18743, 1858 and 30 times greater than that of isoprenaline, salbutamol and formoterol, respectively. 5. Relaxant responses of guinea-pig trachea to S1319 declined rapidly when the agonist was washed from the tissues, with complete recovery within 30 min. The duration of action of S1319 was similar to that of isoprenaline and less than that of salbutamol and formoterol. 6. In summary, S1319, a sponge-derived beta-adrenoceptor agonist, is a potent and selective beta2-adrenoceptor agonist with a short-duration of action in isolated guinea-pig tracheas.

Adrenergic beta-Agonists↗

Site-directed mutagenesis of two zinc-binding centers of the NADH-dependent phenylacetaldehyde reductase from styrene-assimilating Corynebacterium sp. strain ST-10.

Phenylacetaldehyde reductase (PAR) with a unique and wide substrate range from styrene-assimilating Corynebacterium sp. strain ST-10, which is a useful biocatalyst producing chiral alcohols, has been found to belong to a family of zinc-containing, long-chain alcohol dehydrogenases (ADHs) on the basis of the primary structure similarity. The enzyme contains 2 moles of zinc per mole of subunit. The amino acid residues assumed to be three catalytic and four structural zinc-binding ligands were characterized by site-directed mutagenesis, compared with other zinc-containing, long-chain ADHs. Sixteen PAR mutants gave measurable but rather low activities toward phenylacetaldehyde, n-hexyl aldehyde, and 2-heptanone, although they maintained the activities of 8 to 16% of that of wild-type PAR for an acetophenone substrate except that the D153N mutant showed quite low activity. The results suggested that the seven residues present in PAR were probably zinc-binding ligands, and mutation in these residues caused a change in activities for some substrates.

Alcohol Oxidoreductases↗

Non-surgical reduction of septal myocardial mass in a patient with hypertrophic obstructive cardiomyopathy.

Non-surgical reduction of septal myocardial mass was performed with success in a 48-year-old male with hypertrophic obstructive cardiomyopathy. Angioplasty balloon inflated in the first septal branch of the left anterior descending artery dramatically reduced the pressure gradient across the outflow tract of the left ventricle. Following injections of absolute alcohol into the artery with the balloon kept inflated induced a small septal myocardial infarction. By hemodynamic evaluation, the peak pressure gradient of 108 mmHg before the procedure was decreased to 30 mmHg. Clinical improvement in New York Heart Association (NYHA) functional class was obtained. At 3-month follow-up, the patient was doing quite well; the gradient was only 10 mmHg at rest and 25 mmHg with Valsalva maneuver.

Angioplasty, Balloon↗

Specialty-related disparities of readmission in patients with chronic heart failure: the importance of hospital-clinic cooperation.

OBJECT: The purpose of this study was to elucidate differences in readmission rates and late outcome in outpatients with chronic heart failure treated in different clinical settings. PATIENTS AND METHODS: This study included 65 consecutive patients who were admitted to our CCU due to acute heart failure for the first time and discharged from our institution. After their discharge, 31 were cared for by a cardiologist in the outpatient clinic of our institution (group A) and the other 34 were cared for by a general practitioner in a clinic (group B). The various findings during the acute phase and the follow-up period were retrospectively compared between the two groups. In addition, the incidence of unexpected readmission and prolonged outcomes were compared between the two groups. RESULTS: The patients in group B were older than those in group A, but no other differences were noted in patient characteristics. More patients in group A required more than one hospitalization within 6 months from discharge (group A, 35.5%; group B, 8.9%, p<0.01; follow-up period, 17.1+/-5.9 months). There was no difference in the survival rate between the groups. CONCLUSION: We concluded that stabilized outpatients should receive comprehensive care from a general practitioner to avoid the need for readmission after discharge.

Aged↗

[Percutaneous transluminal septal ablation with ethanol in hypertrophic obstructive cardiomyopathy: a case report].

A 48-year-old man with hypertrophic obstructive cardiomyopathy was treated by nonsurgical septal ablation. He had previously received medical treatment using atenolol and verapamil, but severe symptoms of chest discomfort, dyspnea, and shortness of breath had persisted for 2 years. Under coronary angiography control, the first major septal branch of the anterior descending coronary artery was catheterized with a 2.0 mm coaxial percutaneous transluminal coronary angioplasty balloon catheter. After inflation of the balloon, 1.5 ml of absolute alcohol was slowly injected into the septal artery to induce a small septal infarction. The left ventricular outflow pressure gradient was decreased from 108 before to 30 mmHg after the procedure as measured by Doppler echocardiography. His chest symptom improved from New York Heart Association class III to II and left ventricular outflow gradient was maintained at 0 mmHg (at rest) at 3 months after treatment. This is a new, less invasive treatment using catheterization instead of surgical myectomy. The indication, complication, and long-term effect of the treatment must be carefully evaluated, but this is expected to become a useful method.

Angioplasty, Balloon, Coronary↗

[Immunohistochemical study of Sertoli-stromal cell tumor; comparison between the tumor arising from the gonad of a testicular feminization syndrome bearing patient and from ovaries of non-bearing patients].

The association of Sertoli-stromal cell tumor with testicular feminization syndrome (TFS) has been elaborated in the past studies. Here, we described immunohistochemical studies on Sertoli cell tumor of the gonad in a TFS patient and compare with 2 other cases of spontaneous ovarian Sertoli-stromal tumor. [Case 1] The case was a 73 year-old Japanese patient (46XY karyotype), who had had primary amenorrhea. High level of testosterone was noted in laboratory investigation (1900 ng/ml). No ambiguous morphology of external genitalia was present, but atrophy of vagina was noted. The patient was diagnosed as TFS. A left gonadal tumor was identified histologically showing well differentiated Sertoli cell tumor. The tumor cells were positive for anti-vimentin antibody but negative for anti-keratin, EMA and p53 antibodies by immunohistochemistry. The right gonad was an immature testis. [Case 2] The case was a 33 year-old female with ovarian Sertoli-Leydig cell tumor. Immunohistochemically, positive reaction for anti-keratin and p53 antibodies were observed. [Case 3] The case was a 17 year-old female with moderately differentiated Sertoli cell tumor of the ovary. The tumor cells were positive for anti-keratin, EMA and p53 antibodies by immunohistochemistry. Difference in immunohistochemical reactions between Sertoli cell tumor in TFS and Sertoli-stromal cell tumors of the ovaries was probably due to variation in the degree of gonadal development.

Adolescent↗